Structural Basis for Membrane Targeting of the BBSome by ARL6

The BBSome is a coat-like ciliary trafficking complex composed of proteins mutated in Bardet-Biedl syndrome (BBS). A critical step in BBSome-mediated sorting is recruitment of the BBSome to membranes by the GTP–bound Arf-like GTPase ARL6. We have determined crystal structures of C. reinhardtii ARL6–...

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Main Authors:	Mourão, André, Nager, Andrew R., Nachury, Maxence V., Lorentzen, Esben
Format:	Online
Language:	English
Published:	2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255524/

id	pubmed-4255524
recordtype	oai_dc
spelling	pubmed-42555242015-06-01 Structural Basis for Membrane Targeting of the BBSome by ARL6 Mourão, André Nager, Andrew R. Nachury, Maxence V. Lorentzen, Esben Article The BBSome is a coat-like ciliary trafficking complex composed of proteins mutated in Bardet-Biedl syndrome (BBS). A critical step in BBSome-mediated sorting is recruitment of the BBSome to membranes by the GTP–bound Arf-like GTPase ARL6. We have determined crystal structures of C. reinhardtii ARL6–GDP, ARL6–GTP and the ARL6–GTP–BBS1 complex. The structures demonstrate how ARL6–GTP binds the BBS1 β-propeller at blades 1 and 7 and explain why GTP– but not GDP–bound ARL6 can recruit the BBSome to membranes. Single point mutations in the ARL6–GTP–BBS1 interface abolish the interaction of ARL6 with the BBSome and prevent the import of BBSomes into cilia. Furthermore, we show that BBS1 with the M390R mutation, responsible for 30% of all reported BBS disease cases, fails to interact with ARL6–GTP providing a molecular rationale for patient pathologies. 2014-11-17 2014-12 /pmc/articles/PMC4255524/ /pubmed/25402481 http://dx.doi.org/10.1038/nsmb.2920 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mourão, André Nager, Andrew R. Nachury, Maxence V. Lorentzen, Esben
spellingShingle	Mourão, André Nager, Andrew R. Nachury, Maxence V. Lorentzen, Esben Structural Basis for Membrane Targeting of the BBSome by ARL6
author_facet	Mourão, André Nager, Andrew R. Nachury, Maxence V. Lorentzen, Esben
author_sort	Mourão, André
title	Structural Basis for Membrane Targeting of the BBSome by ARL6
title_short	Structural Basis for Membrane Targeting of the BBSome by ARL6
title_full	Structural Basis for Membrane Targeting of the BBSome by ARL6
title_fullStr	Structural Basis for Membrane Targeting of the BBSome by ARL6
title_full_unstemmed	Structural Basis for Membrane Targeting of the BBSome by ARL6
title_sort	structural basis for membrane targeting of the bbsome by arl6
description	The BBSome is a coat-like ciliary trafficking complex composed of proteins mutated in Bardet-Biedl syndrome (BBS). A critical step in BBSome-mediated sorting is recruitment of the BBSome to membranes by the GTP–bound Arf-like GTPase ARL6. We have determined crystal structures of C. reinhardtii ARL6–GDP, ARL6–GTP and the ARL6–GTP–BBS1 complex. The structures demonstrate how ARL6–GTP binds the BBS1 β-propeller at blades 1 and 7 and explain why GTP– but not GDP–bound ARL6 can recruit the BBSome to membranes. Single point mutations in the ARL6–GTP–BBS1 interface abolish the interaction of ARL6 with the BBSome and prevent the import of BBSomes into cilia. Furthermore, we show that BBS1 with the M390R mutation, responsible for 30% of all reported BBS disease cases, fails to interact with ARL6–GTP providing a molecular rationale for patient pathologies.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255524/
_version_	1613163854673477632

Structural Basis for Membrane Targeting of the BBSome by ARL6

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